SAT0490 MATCHED CONTROLLED SURVEILLANCE OF TOCILIZUMAB TREATMENT FOR POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS–AN INTERIM ANALYSIS
Authors: A. Klein, T. Hospach, F. Weller-Heinemann, S. Hansmann, J. Kuemmerle-Deschner, M. Fasshauer, K. Minden, I. Foeldvari, C. Rietschel, T. Schwarz, R. Trauzeddel, M. Hufnagel, D. Foell, R. Berendes, G. Boeschow, P. Oommen, F. Dressler, A. Helling-Bakki, G. Horneff
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tocilizumab (TOC) is approved for treatment of polyarticular juvenile idiopathic arthritis (pJIA). Data out of clinical practice are limited. Objectives: Long-term surveillance of patients initiating TOC treatment compared to a cohort of patients initiating a comparator biologic using the BIKER-registry. Methods: Baseline parameters, efficacy and safety parameters were compared. Efficacy outcomes were JADAS10 and joint counts. Functional status was determined with the Childhood Health Assessment Questionnaire disability-index (CHAQ-DI). Safety was assessed by adverse events (AE) reports. Results: Until January 2020, 152 patients have been recruited to each cohort. Patients starting on TOC were older at treatment start (12.1 vs. 10.1 years (y); p&lt;0.0001) and had a longer disease duration (5.4y vs. 3.0y; p&lt;0.0001). TOC was significantly more often a second-line biologic (84% vs 13%, p&lt; 0.0001). Otherwise patients were comparable (Table 1). Table 1. Comparison of TOC patients and matched controls. Tocilizumab N=152 Matched controls N=152 p Gender female, n (%) 128 (84) 124 (81) 0.65 Disease duration, mean (SD), years 5.4 (4.1) 3.0 (2.9) &lt;0.0001 RF neg. polyarthritis, n (%) 104 (68.4) 92 (60.5) 0.19 RF pos. polyarthritis, n (%) 14 (9.2) 19 (12.5) 0.46 Extended oligoarthritis, n (%) 34 (22.4) 41 (27) 0.42 Pretreatment with biologics, n(%) 127 (83.5) 20 (13.2) &lt;0.0001 Active joint count, mean (SD) 6.7 (7.1) 6.1 (5.1) 0.4 CHAQ DI, mean (SD) 0.63 (0.63) 0.65 (0.64) 0.8 ESR, mm/h, mean (SD) 17.5 (14.9) 20.9 (20.6) 0.1 JADAS10, mean (SD) 16.8 (9.8) 15.1 (5.8) 0.067 Efficacy Month 12 N=87 N=105 JADAS MDA, n (%) 50 (57.5) 63 (60.0) 0.77 JADAS REM, n (%) 32 (36.8) 39 (37.1) 1.0 JIA ACR 30/50/70/90, % 80/75/61/53 86/84/70/56 0.34/0.15/0.17/0.66 Adverse events N (rate/100PY; 95%CI ) 248,65 PY 290.4 PY RR (95%CI); p AE 145 (58.3; 50-69) 157 (54.1; 46-63) 1.1 (0.9-1.4); 0.5 SAE 12 (4.8; 2.7-8.5) 4 (1.4; 0.5-3.7) 3.5 (1.1-10.9); 0.03 Medically important infection 2 (0.8; 0.2-3.2) 12 (4.1; 2.3-7.3) 0.2 (0.04-0.9); 0.03 Uveitis event 2 (0.8; 0.2-3.2) 12 (4.1; 2.3-7.3) 0.2 (0.04-0.9); 0.03 Upon TOC a substantial response to treatment with a significant reduction in JADAS 10 from 16.8 to 3.4 (p&lt;0.0001) after 12 months was observed. There were no significant differences between patients from the TOC cohort and their matched controls regarding JIA ACR 30/50/70/90 criteria and active joint counts. JADAS 10, JADAS remission (REM) and minimal disease activity (MDA) was reached by comparable numbers in the TOC (37% and 58%) and the control cohort (37% and 60%). While the total number of AE was comparable between the TOC cohort (58/100PY) and in the control cohort (54/100PY; RR 1.1; 95%CI 0.9-1.4), more serious AE (SAE) were reported with TOC (4.8/100PY compared to 1.4/100PY; RR 3.5; 95% CI 1-10.9). Medically important infections and uveitis events were documented at significantly lower frequency in the TOC- (0.8/100PY) than in the control cohort (4.1/100PY; RR 0.2; 95% CI 0.04-0.9). SAE with TOC were suicidal intent (n=3), depression (n=2), exacerbation of JIA, abscess, gastrointestinal infection, abdominal pain, colitis, bone surgery and fracture (n=1). SAE in the control cohort were depression, osteomyelitis, gastrointestinal infection and superinfected eczema (n=1). No significant differences regarding cytopenia and elevated transaminases were observed. No gastrointestinal perforation, no vascular event, no malignancy and no death occurred. Conclusion: The efficacy of tocilizumab is comparable to that of alternative biologics. Tolerability was acceptable. As Tocilizumab was given as a second-line biologic in the vast majority of patients, comparisons between the cohorts have to be interpreted carefully. Observation in the registry is ongoing. Disclosure of Interests: Ariane Klein Consultant of: Celgene, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Sandra Hansmann Consultant of: Advisory board Novartis Pharma, Jasmin Kuemmerle-Deschner Grant/research support from: Novartis, Sobi, Consultant of: Novartis, Sobi, Speakers bureau: Novartis, Sobi, Maria Fasshauer Consultant of: Shire, CSL Behring, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Ivan Foeldvari Consultant of: Novartis, Christoph Rietschel Consultant of: Pfizer, Abbvie, Novartis, Chugai, and Sobi, Tobias Schwarz: None declared, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell Grant/research support from: Novartis, Sobi, Pfizer, Speakers bureau: Novartis, Sobi, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prasad Oommen Consultant of: Novartis, Frank Dressler: None declared, Astrid Helling-Bakki: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche